Effect of temperature on toxicity and cardiac chronotropic action of sympathicotropic drugs

Richard K. Richards, M. Eric Gershwin, N. Ty Smith

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The effect of increased temperature on the i.v. toxicity of adrenergic stimulating or blocking agents was studied in mice. The toxicity of epinephrine increased 14.4 times when the environmental temperature was raised from 23° to 35°C; the Q'10 = [1/Q10] being 9.2. Norepinephrine became 2.3 times more toxic, [Q'10=2.4]. This appears to be the greatest quantitative difference in activity reported between these two amines. The alpha-stimulators phenylephrine and methoxamine also showed marked increases in toxicity and high Q'10 values of 6.6 and 1.86, respectively, but not tyramine, the beta-stimulator isoproterenol, or the adrenergic blocking agents dichlorisoproterenol, phenoxybenzamine and propranolol. Effects of these drugs on the contraction rate of isolated guinea-pig atria was determined at temperature intervals of 2°C, between 32°-42°C. All beta-stimulating compounds caused rate increases composed of temperature and drug effects, but only epinephrine at 1.17 × 10-4 mM concentration changed the slope of the dose-effect curve. Phenylephrine, phenoxybenzamine and propranolol failed to influence the rate at any temperature studied.

Original languageEnglish (US)
Pages (from-to)289-296
Number of pages8
JournalEuropean Journal of Pharmacology
Volume9
Issue number3
DOIs
StatePublished - 1970
Externally publishedYes

Keywords

  • Alpha-adrenergic receptors
  • Beta-adrenergic receptors
  • Catecholamines
  • Drug toxicity
  • Environmental temperature
  • Heart rate
  • Q
  • Sympathicotropic drugs

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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